1. Field of the Invention
The present invention relates to apparatus and a method for the rapid preparation of a radiopharmaceutical formulation.
2. Description of the Prior Art
Technetium Tc.sup.99 m-Sestamibi is a technetium-labeled radiopharmaceutical that is manufactured by DuPont-Merck Pharmaceutical Company, Billerica, Mass., and sold under the trademark Cardiolite.RTM.. Technetium Tc.sup.99 m-Sestamibi finds primary utility as a myocardial imaging agent.
A formulation of the technetium-labeled radiopharmaceutical imaging agent is prepared for use by injecting a volume (on the order of approximately one to three milliliters) of a non-pyrogenic sodium pertechnetate Tc.sup.99 m solution derived from a generator into a vial containing a lyophilized form of other non-radioactive ingredients [particularly, appropriate amounts of (2-methoxy isobutyl isonitrile) copper tetrafluoroborate, sodium citrate dihydrate, cysteine hydrochloride monohydrate, mannitol and stannous chloride dihydrate]. The vial is itself placed in a suitable radiation shield, typically a cylindrical can-like member with a fitted cap. Label instructions require that after injection the vial containing the mixture of the sodium pertechnetate and the lyophilized non-radioactive ingredients be removed from the radiation shield, and heated in a boiling water bath for at least ten minutes. After heating in the boiling bath the vial is returned to the shield for a cool-down period of approximately fifteen minutes. A radiochemical purity analysis is performed to insure that the radiopharmaceutical formulation so prepared exhibits the desired labeling efficiency prior to use.
These timing restrictions on the preparation of Technetium Tc.sup.99 m-Sestamibi radiopharmaceutical formulation may, in instances such as emergency cases, limit its availability. In order to reduce the preparation time and, consequently, enhance the availability of Technetium Tc.sup.99 m-Sestamibi imaging formulation, several alternative methods of its preparation have been proposed.
One method, discussed in the article by Tallifer, Gagnon, Lambert and Levilie, "Labeling procedure and in-vitro stability of Tc99m methoxy isobutyl isonitrile (MIBI): practical considerations", appearing at J Nucl Med 1989; 30; 865 (abs), demonstrates that bath times as low as one (1) minute may be sufficient to provide a Technetium Tc.sup.99 m-Sestamibi solution having an acceptable labeling efficiency and a radiochemical purity in excess of ninety percent. However, this method still requires a significant amount of time (on the order of ten to twenty-five minutes) be expended to heat to boil the water used for the immersion bath. Thus, the time gain obtained from the reduction in the actual immersion time is lost because time is still required to heat the water for the immersion bath.
Other proposed methods of preparation of Technetium Tc.sup.99 m-Sestamibi formulation have focused on the use of alternative heat sources. Several alternative methods discuss the use of a microwave oven as the source of heat. Microwave heating methods are discussed in an article by Gagnon, Tallifer, Bavaria and Levilie, "Fast labeling of technetium-99m-sestamibi with microwave oven heating", J Nucl Med Technol 1991; 19; 90-3, and in an article by Hung, Wilson, Brown and Gibbons, "Rapid preparation and quality control method for technetium-99m-2 methoxy isobutyl isonitrile (technetium-99m sestamibi)", J Nucl Med 1991; 32; 2162-8. Another method, discussed in a letter by Wilson, Hung and Gibbons, "Simple procedure for microwaved technetium-99m sestamibi temperature reduction", J Nucl Med Technol 1992; 20; 180, focuses on a technique for the rapid cooling of the heated Technetium Tc.sup.99 m-Sestamibi formulation.
Although microwave oven-based heating methods appear to overcome some of the obstacles presented in the preparation of Technetium Tc.sup.99 m-Sestamibi formulation, such methods appear also to exhibit serious attendant drawbacks, such as vial breakage (as outlined in a letter by Hung and Gibbons, "Breakage of technetium-99m sestamibi vial with the use of a microwave oven", J Nucl Med 1992; 33; 176-8). Other perceived problems with the microwave oven-based heating technique are set forth in an article by Wilson, Hung and Gibbons, "An alternative method for rapid preparation of .sup.99 Tc.sup.m -sestamibi", Nucl Med Commun 1993; 14; 544-9. This latter article proposes an alternative heating method involving the use of an instant hot water machine as the source of heated water used for the preparation of Technetium Tc.sup.99 m-Sestamibi formulation.
Other heating sources for raising the temperature of materials used in connection with life science reactions are known in the art. For example, an apparatus manufactured by MJ Research, Inc, Watertown, Mass. and sold as "The MiniCycler.TM. programmable thermal controller" utilizes a heating/cooling element driven by the thermoelectric effect to both heat and cool samples for various biotechnological reactions. The basic operating principle of a thermoelectric heating/cooling element is the Peltier Cooling Effect, in which heat is absorbed or generated as a current passes through a junction of two dissimilar materials. Electrons passing across the junction absorb or give up an amount of energy equal to the transport energy and the energy difference between the dissimilar-materials conduction bands.
The materials to be heated or cooled in the programmable thermal controller apparatus are typically carried in microultracentrifuge tubes, also known as "Eppendorf Tubes", or in other suitable reaction tubes. The programmable thermal controller includes a sample block in which a plurality of wells are formed. Each tube carrying a sample therein is inserted into a well, and the appropriate heating and/or cooling program initiated. Each of the wells formed in the sample block corresponds in configuration to the exterior configuration of the container inserted therein. Use of the programmable thermal controller in connection with radioactive reactions appears to be contemplated.
In view of the foregoing it is believed advantageous to utilize a thermoelectric (Peltier-effect) heating/cooling element to precisely control both heating and cooling of Technetium Tc.sup.99 m-Sestamibi imaging formulation, thereby to make preparation of an effective dosage of the imaging formulation rapidly available for use in emergency and other situations.